The present invention relates generally to a method for coating, at least regions of, a medical implant, preferably of an artificial joint or a fixation for a joint.
The present invention also relates generally to a device for coating, at least regions of, a medical implant using the method.
The coating of medical implants with pharmaceutical agents has garnered increasing attention in recent years. Antibiotic protection of the surface of implant materials is a central application of coating methods in this context. The improvement of the surface compatibility of non-cemented medical implants in order to improve osseointegration is another important application.
Any implantation of articular endoprostheses, and of osteosynthesis materials as well, is associated with a certain risk of microbial contamination. Successful colonization of microbial pathogens on the surface of the implant can lead to the manifestation of post-operative osteitis/osteomyelitis. Osteitis/osteomyelitis is a severe complication for the patient and, in addition, is associated with substantial costs.
Gentamicin-doped PMMA bone cement has been in clinical use with cemented articular endoprostheses for decades with much success. The broadband antibiotic, gentamicin, contained in the bone cement protects the surface of the bone cement effectively from bacterial infections.
With regard to non-cemented articular endoprostheses and osteosynthesis materials, a number of approaches has been proposed in order to also attain local antibiotic protection of the implant surfaces.
For example, the use of poorly water-soluble antibiotic salts has been described in several patent documents. For exemplary purposes, EP 0 623 349 A1, EP 1 470 829 A1, EP 1 374 923 A2, DE 101 42 465 A1, and DE 44 04 018 A1 can be cited in this context. The poorly water-soluble salts dissolve while releasing the antibiotics contained therein as a result of the action of body fluids. Prolonged release of the agent is advantageous. However, the laborious production of the salts is disadvantageous.
Alternatively, it is feasible to use water-soluble antibiotic salts. This is associated with a problem related to fixation of the antibiotic on the implant surface.
The majority of coatings that have been described thus far is preferably intended for the manufacture of coated implants under industrial conditions. This means that the industrial coating of the implants can only involve few agents that are relevant for large-scale use in order to be able to guarantee that the industrial manufacture is economic through sufficiently large throughput.
In particular in the case of antibiotic coatings, though, considering the increasingly problematic resistance status and the ensuing increased manifestation of multi-resistant pathogens, such as MRSA and MRSE, it is of interest to use antibiotics or combinations of antibiotics, which are specifically adapted to the germ at hand, for the coating of revision prostheses in one-stage or two-stage septic articular endoprosthesis replacement in order to ensure effective initial antibiotic protection of the implant surfaces.
This is disadvantageous in that the methods for coating the medical implants are relatively laborious. Variable short-term application is not feasible. Various scenarios then necessitate the stock-keeping of various coated medical implants in order to meet the needs of the different patients. This requires extensive stock-keeping and prevents uncommon mixtures for specific cases.
In general, non-cemented articular endoprostheses are made from titanium alloys and usually have a surface that is roughened (for example through sand-blasting) or structured and porous in order to improve the integration of bone tissue. The alloys used thus provide for assured mechanical stability and integrity. For this reason, it was attempted to improve the compatibility of the implant surfaces with respect to the bone tissue. The mineral phase of human bone tissue is provided by a carbonate apatite/hydroxyl apatite. Therefore, the main emphasis of improving the compatibility of surfaces of medical implants is on the development of calcium phosphate layers.
A broad range of methods (thermal injection procedures, electrochemical deposition, sol-gel technologies, ion beam sputtering, laser ablation) have been used in attempts to attain an improvement of the surface compatibility at the contact site with the bone tissue (hip, knee, shoulder joint endoprostheses). Thus far, on an industrial scale, only the plasma spraying procedure (De Groot et al.: Plasma-sprayed coatings of calcium phosphate. CRC Press, Boca Raton, Ann Arbor, Boston, 1990; De Groot et al.: Chemistry of calcium phosphate bioceramics. CRC Handbook of bioactive ceramics, 2, 1996, 3-16; WO 2009/062671 A2) and electrochemical deposition of calcium phosphate layers (Ban and Maruno: Morphology and microstructure of electrochemically deposited calcium phosphates in a modified simulated body fluid. Biomaterials, 19, 1998, 1245-1253; DE 44 31 862 A1; WO 2009/147045 A1; CN 101485901 A; CN 101406711 A; WO 2007/147246 A1; US 2006/134160 A1; WO 2004/098436 A2; WO 2004/024201 A2; EP 1 264 606 A1; EP 0 232 791 A2) have become established. Printed publications US 2002/110541 A1, U.S. Pat. No. 5,807,567 A, US 2002/197315 A1, U.S. Pat. No. 6,652,887 B1, U.S. Pat. No. 5,756,127 A, and U.S. Pat. No. 5,614,206 A describe bone replacement materials which essentially consist of a mixture of α- and β-calcium phosphate and are designed for use as “drug delivery” systems for pharmaceutical agents.
However, clinical long-term studies have shown that plasma-sprayed calcium phosphate layers, although generally considered to be stable in the long term, are subject to partial degradation in their biological environment. There are not only phase changes at the boundary to the bone tissue, but also the process leads to encapsulation and/or flaking off, predominantly of crystalline components of the layer, and thus to interfering particles.
It is another disadvantage that all electrochemical deposition methods that are common thus far necessitate a substantial equipment and time effort in order to be able to apply the calcium phosphate layers to the articular endoprosthesis.